The aim of the proposed project is to make a systematic study of the effects of immaturity and asphyxia upon fetal pharmacokinetics and responsed anesthetics and related drugs commonly administered to parturinets (local anesthetics, narcotics and barbituates). With the increased incidence of cesarean delivery in the management of premature labor and fetal distress, greater numbers of immature and asphyxiated fetuses are exposed to anesthetic agents. The principal hypothesis to be tested is that in these fetuses the kinetics and effects of drugs transmittd across the placenta may be altered. Chronically prepared pregnant sheep will receive a constant-rate intravenous infusion of three representative agents, viz., lidocaine, meperidine and pentobarbital. Infusions will be maintained over a period of four terminal phase half-lives to achieve steady-state drug concentrations in the maternal arterial blood similar to those occurring in clinical practice. Drug levels will be determined in maternal and fetal blood and urine, and in fetal tissues. Maternal and fetal heart rate, blood pressure and acid-base state will be monitored. Uterine blood flow, fetal cardiac output and its tissue distribution will be determined. Animals will be studied in four groups according to fetal condition: immature, mature, asphyxiated, nonasphyxiated. Data obtained from these four groups of moterhs and fetuses will be compated, using appropriate statistical methods. It is hoped that these studies will provide a rational basis for the management of "high risk" fetuses.